Inula britannica is a traditional Chinese medicinal herb that has been used to treat bronchitis and inflammation. A variety of this plant, known as Inula britannica chinensis has been used as an insecticide in certain areas of China. Both Inula britannica and Inula britannica chinensis have been examined in order to determine the chemical constituents responsible for its pharmacological effects. A variety of sesquiterpenes have been isolated. In the case of Inula britannica chinensis, three specific sesquiterpene lactones were identified, including britannilactone, 1-O-acetylbritannilactone, and 1,6-O,O-diacetylbritannilactone (Zhou, B-N. et al. 1993. Phytochemistry 34:249-252).
Some natural plant extracts have been shown to have activity as chemopreventive agents. An example, taxol, acts by inducing Bcl-2 phosphorylation in cancer cells which leads to programmed cell death (Haldar, S. Et al. 1996. Cancer Res. 56:1253-1255). The Bcl-2 protein is a member of a family of cytoplasmic proteins which regulates cell death. Bcl-2 has been shown to promote cell survival by inhibiting the process of cell death known as apoptosis. Whereas Bcl-2 acts to inhibit apoptosis, Bax, another cytoplasmic protein, counteracts this protective effect; Bcl-2 is also thought to protect cells from apoptosis by dimerizing with Bax (Hunter, J. J. et al. 1996. J. Biol. Chem. 271:8521-8524). The phosphorylation of Bcl-2 interferes with the homodimers and subsequent apoptosis (Haldar, S. et al. 1995. Proc. Natl. Acad. Sci. USA 92:4507-4511; Haldar, S. Et al. 1996. Cancer Res. 56:1253-1255). Therefore, therapeutic strategies to inactivate Bcl-2 are being sought as a way to improve clinical results with certain drugs. It has now been found that an extract of Inula britannica has activity relevant to prevention and treatment of cancer due to its activity to phosphorylate Bcl-2.
An object of the present invention is a composition that induces apoptosis in cells which comprises an extract of Inula Britannica or compounds isolated therefrom. In a preferred embodiment the composition comprises sesquiterpene lactone.
Another object of the present invention is a method for inducing apoptosis in cells comprising contacting cells with an extract of Inula Britannica or compounds isolated therefrom so that apoptosis is induced.
Yet another object of the present invention is a method for preventing and treating cancer which comprises administering an effective amount of extract of Inula Britannica or compounds isolated therefrom.